The vast majority of sensory neurons in the trachea are of vagal origin and expressing CGRP which is involved as modulator in several nocifensive tracheal reactions. The isolated mouse trachea allows to measure (by EIA) basal and stimulated CGRP release which serves as an index for (chemo-) sensory transduction mechanisms. (S-) - nicotine is an obvious irritant to the trachea and showed an inversely U - shaped concentration – response (ED50~30mM); its effect was fully antagonized by mecamylamine but not methyllycaconitine, suggesting an a3b4 composition of the responsible nicotinic receptor. At 10 mM, nicotine induced an unexpected magnitude of CGRP release that was absent in TRPV1 knockout mice, indicative for a capsaicin - like action. Established TRPA1 agonists icilin, mustard and cinnamon oil, most potently acrolein, a smoke constituent, induced concentration - dependent CGRP release, which effects were retained in TRPV1-/- and blocked by camphor (2mM). Both findings applied also to menthol 10 mM, which concentration is supramaximal to TRPM8 and indicates additional TRPA1 activation by menthol. Relevant to the tracheal pathophysiology, bradykinin (10 mM) also induced CGRP release fully retained in TRPV1-/- and reduced by camphor, which is in contrast to the skin where bradykinin seems to act through sensitizing both, TRPV1 and TRPA1.